A General Functional Response of Cytotoxic T Lymphocyte-Mediated Killing of Target Cells
A General Functional Response of Cytotoxic T Lymphocyte-Mediated Killing of Target Cells
复制标题
DOI：
10.1016/j.bpj.2014.01.048
复制
发表时间：
2014-04-15
影响因子：
3.4
通讯作者：
de Boert, Rob J.
中科院分区：
文献类型：
--
作者：
Gadhamsetty, Saikrishna;Maree, Athanasius F. M.;de Boert, Rob J.
细胞毒性T淋巴细胞（CTL）可杀死病毒感染的细胞和肿瘤细胞，在免疫保护中发挥关键作用。我们对 CTL 杀伤效率如何随 CTL 和靶细胞数量变化的了解有限。在这里，我们使用细胞 Potts 模型模拟淋巴组织区域来表征 CTL 杀伤靶细胞的功能反应，并发现总杀伤率随着 CTL 和靶细胞密度的增加而饱和。 CTL和靶细胞密度的相对饱和度取决于一个CTL是否可以同时杀死多个靶细胞，以及一个靶细胞是否可以被多个CTL一起杀死。我们发现所有研究的情况都可以通过具有两个不同饱和常数的双饱和（DS）函数来很好地描述。我们表明，对于靶细胞被单个 CTL 杀死的情况，可以从机制上推导出该 DS 模型。对于其他情况，参数的生物学解释仍然是可能的。我们的结果表明该 DS 函数可用作预测细胞毒性数据中细胞相互作用的工具。
Cytotoxic T lymphocytes (CTLs) kill virus-infected cells and tumor cells, and play a critical role in immune protection. Our knowledge of how the CTL killing efficiency varies with CTL and target cell numbers is limited. Here, we simulate a region of lymphoid tissue using a cellular Potts model to characterize the functional response of CTL killing of target cells, and find that the total killing rate saturates both with the CTL and the target cell densities. The relative saturation in CTL and target cell densities is determined by whether a CTL can kill multiple target cells at the same time, and whether a target cell can be killed by many CTLs together. We find that all the studied regimes can be well described by a double-saturation (DS) function with two different saturation constants. We show that this DS model can be mechanistically derived for the cases where target cells are killed by a single CTL. For the other cases, a biological interpretation of the parameters is still possible. Our results imply that this DS function can be used as a tool to predict the cellular interactions in cytotoxicity data.